From the Division of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, Tohoku University School of Medicine, Sendai, Japan (S.I.).
Department of Endocrinology, Metabolism and Nephrology, Keio University, School of Medicine, Tokyo, Japan (H.I.).
Hypertension. 2020 Jan;75(1):51-58. doi: 10.1161/HYPERTENSIONAHA.119.13569. Epub 2019 Dec 2.
Mineralocorticoid receptors (MRs) are implicated in the pathology of hypertension. MR blockers are recommended for the treatment of salt-sensitive or resistant hypertension. However, use of currently available MR blockers is limited by adverse events. This phase 3 multicenter, randomized, double-blind study compared the efficacy and safety of esaxerenone, a new selective nonsteroidal MR blocker, at 2.5 and 5 mg/day and eplerenone 50 mg/day in Japanese patients with essential hypertension. After a 4-week washout period, 1001 eligible adults with hypertension were randomized evenly to esaxerenone 2.5 or 5 mg/day or eplerenone 50 mg/day treatments, taken orally once daily for 12 weeks. Primary end points were changes in sitting systolic or diastolic blood pressure (BP) from baseline at the end of treatment. Esaxerenone 2.5 mg/day was noninferior to eplerenone for reductions in sitting and 24-hour BP. Reductions in BP with esaxerenone 5 mg/day were significantly greater than those with esaxerenone 2.5 mg/day. Changes in diurnal BP showed persistent 24-hour antihypertensive effects in all treatment groups. The proportions of patients achieving target sitting BP (<140/90 mm Hg) were 31.5%, 41.2%, and 27.5% with esaxerenone 2.5 and 5 mg/day and eplerenone 50 mg/day, respectively. Incidences of adverse events (all mild or moderate) were similar across treatment groups. These results indicate that esaxerenone is an effective and well-tolerated MR blocker in Japanese patients with essential hypertension, with BP-lowering activity at least equivalent to eplerenone. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT02890173.
矿皮质激素受体 (MRs) 与高血压的发病机制有关。MR 阻滞剂被推荐用于治疗盐敏感或耐药性高血压。然而，目前可用的 MR 阻滞剂的使用受到不良反应的限制。这项 3 期多中心、随机、双盲研究比较了新型选择性非甾体 MR 阻滞剂 esaxerenone 在 2.5 和 5 mg/天以及依普利酮 50 mg/天剂量治疗日本原发性高血压患者的疗效和安全性。经过 4 周的洗脱期后，1001 名符合条件的高血压成年患者被平均随机分为 esaxerenone 2.5 或 5 mg/天或依普利酮 50 mg/天组，每日口服一次，治疗 12 周。主要终点是治疗结束时与基线相比坐位收缩压或舒张压 (BP) 的变化。esaxerenone 2.5 mg/天与依普利酮相比，坐位和 24 小时 BP 的降低均不劣效。esaxerenone 5 mg/天的 BP 降低显著大于 esaxerenone 2.5 mg/天。日间 BP 的变化显示所有治疗组均具有持续 24 小时降压作用。达到坐位 BP 目标(<140/90 mm Hg)的患者比例分别为 esaxerenone 2.5 和 5 mg/天组为 31.5%、41.2%和依普利酮 50 mg/天组为 27.5%。不良反应的发生率（均为轻度或中度）在各组之间相似。这些结果表明，esaxerenone 是一种有效且耐受良好的 MR 阻滞剂，在日本原发性高血压患者中具有至少与依普利酮相当的降压活性。临床试验注册- URL：http://www.clinicaltrials.gov。唯一标识符：NCT02890173。
